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Here, ionizable coenzyme Q10 (iCoQ10)\u2010engineered lipid\/fiber microplexes (iCLNP@SF) are developed that restore the mitochondrial\u2010ribosomal axis to enhance mRNA translation. iCoQ10 replaces conventional ionizable lipids to form prodrugged lipid nanoparticles (iCLNP), stabilized by injectable polydopamine\u2011modified short fibers for in situ administration. In vitro efficacy assessments showed that iCLNP@SF synergistically enhanced mitochondrial metabolism and mRNA translation in senescent cells. Further mechanistic studies revealed that iCLNP stabilized mitochondrial membrane potential, suppressed cGAS\u2010STING activation, and reduced eIF2\u03b1 phosphorylation, thereby enhancing translation. In vivo, iCLNP@SF delivery of Gas6 mRNA increased hair follicle density by \u224850% in an androgenetic alopecia mouse model, while Runx2 mRNA delivery raised new bone formation (BV\/TV) to \u224840% in defect models, both markedly outperforming conventional LNPs. Together, these findings highlight a strategy that improves mRNA therapy for degenerative diseases.<\/jats:p>","DOI":"10.1002\/adma.202513720","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T08:26:26Z","timestamp":1759911986000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Ionizable Coenzyme\u2010Engineered Lipid\/Fiber Microplexes Boost Ribosomal Translation to Improve mRNA Therapy for Degenerative Diseases"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8388-0688","authenticated-orcid":false,"given":"Shifeng","family":"Ling","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine  197 Ruijin 2nd Road Shanghai 200025 P. R. 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